7. PROJECT SUMMARY/ABSTRACT Perception, cognition, and other high level brain functions are thought to arise in the neocortex, a laminar sheet of neurons forming the surface of the brain. However, the billions of neurons and trillions of synaptic connections in the cortex form an overwhelmingly complex system, and therefore more insight into the organization of the cortex at the local circuit level is needed. Previous research has suggested that ontogenetic columns (columns of clonally-related neurons) play a critical role in excitatory neuron integration in local microcircuitry, and may represent a fundamental module of cortical computation. However, the functional relationships within an ontogenetic column and the principles of ontogenetic column integration into the local circuit of inhibitory interneurons have not been examined. This project will use multi-photon in vivo calcium imaging to characterize the visual feature selectivity of clonally-related neurons across all layers of primary visual cortex, and examine the distribution of feature selectivity within a layer, and how that distribution changes between cortical layers. Additionally, using octuple simultaneous whole cell patching, this project will test different classes of cortical inhibitory interneurons for patterns of connectivity to ontogenetic columns, in order to gain insight into how clonally related neurons integrate with unrelated neurons in the local circuit. Together, these experiments will delineate the influence of ontogenetic history on the functional organization and microcircuitry of adult neocortex. The results of this work have the potential to reveal fundamental new insights into how the brain processes incoming sensory information, and how that information is transformed as it passes from one cortical layer to another. These results will thus enable a more principled understanding of normal and abnormal circuit function, with broad implications for a wide range of currently intractable neuropsychiatric illnesses such as autism and schizophrenia.